Biomedical subjects

A R Elliott

Publications and source records attributed to A R Elliott.

29 records · Page 2Linked to original sources

PubMed1994

Lung volumes during sustained microgravity on Spacelab SLS-1.

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (mu G) on lung volumes has not been reported. Pulmonary function tests were performed by four subjects before, during, and after 9 days of mu G exposure. Ground measurements were made in standing and supine postures. Tests were performed using a bag-in-box-and-flowmeter system and a respiratory mass spectrometer. Measurements included functional residual capacity (FRC), expiratory reserve volume (ERV), residual volume (RV), inspiratory and expiratory vital capacities (IVC and EVC), and tidal volume (VT). Total lung capacity (TLC) was derived from the measured EVC and RV values. With preflight standing values as a comparison, FRC was significantly reduced by 15% (approximately 500 ml) in mu G and 32% in the supine posture. ERV was reduced by 10-20% in mu G and decreased by 64% in the supine posture. RV was significantly reduced by 18% (310 ml) in mu G but did not significantly change in the supine posture compared with standing. IVC and EVC were slightly reduced during the first 24 h of mu G but returned to 1-G standing values within 72 h of mu G exposure. IVC and EVC in the supine posture were significantly reduced by 12% compared with standing. During mu G, VT decreased by 15% (approximately 90 ml), but supine VT was unchanged compared with preflight standing values. TLC decreased by approximately 8% during mu G and in the supine posture compared with preflight standing. The reductions in FRC, ERV, and RV during mu G are probably due to the cranial shift of the diaphragm, an increase in intrathoracic blood volume, and more uniform alveolar expansion.

Adult↗

PubMed1994

Cardiopulmonary adaptation to weightlessness.

The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.

Adaptation, Physiological↗

PubMed1993

Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity.

We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to 9 days of microgravity (weightlessness, 0 G). The same subjects were studied standing and supine numerous times preflight and in the week immediately after return from space. DL in microgravity was elevated (28%) compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc (28%) and Dm (27%). The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value (which was unchanged). We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to 8 days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased (18%) inflight and decreased (9%) post-flight compared with preflight standing. Compared with preflight standing, SV was increased 46% inflight and decreased 14% in the 1st wk postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

Adult↗

PubMed1993

Influence of inhaled anesthetics on the pharmacokinetics and pharmacodynamics of morphine.

We determined the magnitude and duration of the effect of morphine (1.0 mg/kg intravenous bolus) on isoflurane and halothane minimum alveolar concentration (MAC) in six dogs anesthetized on two occasions in cross-over fashion. Plasma morphine concentration-time profiles and changes in PaCO2 were determined after morphine injection. After morphine injection, the end-tidal anesthetic dose was manipulated over the course of a 4-h observation period to account for the decline in plasma morphine concentration and to maintain an anesthetic level equivalent to 1.0 MAC isoflurane or halothane alone. Morphine decreased the MAC of halothane and isoflurane. The magnitude of MAC decrease was related to time after morphine injection and was similar for a given time with both halothane and isoflurane. For example, at 28.8 +/- 3.6 (mean +/- SE) and 34.8 +/- 6.3 min after morphine injection, the MAC for halothane and isoflurane were reduced by 35.7% +/- 4.5% and 39.3% +/- 3.4%, respectively. By 4 h after morphine injection, the MAC reduction for both anesthetics was less than 10% in most of the animals. Except for systemic clearance of morphine during halothane and isoflurane (40.1 +/- 6.1 and 53.7 +/- 5.6 mL.min-1.kg-1, respectively), there were no differences in disposition kinetics of free morphine associated with the two inhaled anesthetics. Morphine increased PaCO2 to a similar degree with both halothane (from 42.2 +/- 2.1 mm Hg to 55.6 +/- 2.3 mm Hg) and isoflurane (46.2 +/- 2.4 mm Hg to 55.3 +/- 2.1 mm Hg). Respiratory depression was abolished by noxious stimulation (tail clamp) and naloxone in all animals with both anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1993

Circulatory and respiratory responses of spontaneously breathing, laterally recumbent horses to 12 hours of halothane anesthesia.

Cardiovascular and respiratory changes that accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, PCV, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2 and PaCO2 did not significantly change during the 12 hours of study, PVO2 increased significantly (P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time (significantly [P < 0.05] starting at 9 hours), despite supplemental IV administered NaHCO3. Plasma concentrations of eicosanoids: 6-keto-prostaglandin F1 alpha (PGF1 alpha, a stable metabolite of PGI2), PGF2 alpha, PGE, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Anesthesia, Inhalation↗

PubMed1992

High lung volume increases stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.

Air Pressure↗

PubMed1992

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure.

We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Unilateral hypoxic pulmonary vasoconstriction in the dog, pony and miniature swine.

The hypoxic pulmonary vasoconstrictor response to unilateral hypoxia was analyzed in pentobarbital anesthetized dogs (n = 5), miniature swine (n = 5), and ponies (n = 5). The left and right lungs (LL, RL) were separately ventilated with the LL exposed to inspired oxygen concentrations (CIO2) of 100%, 12%, 8% or 4%, while the RL always received a CIO2 = 100%. Pulmonary blood flow distribution was measured using 15 microns radioactive microspheres. LL PAO2, and percent pulmonary blood flow diversion (%FD) were calculated at each CIO2. At CIO2 of 4% there were significant differences (P greater than or equal to 0.05) between the %FD responses of each species (mean +/- S.E.): the %FDswine (95.1 +/- 1.3) greater than %FDpony (76.0 +/- 4.6) greater than %FDdog (50.1 +/- 9.4). For all species, the %FD was inversely related to the level of regional hypoxia, but there were marked species differences in the magnitude and sensitivity of hypoxic pulmonary vasoconstriction with the swine being the strongest responder, the pony intermediate, and the dog the weakest responder.

Animals↗

PubMed1991

Maximum expiratory flow-volume curves during short periods of microgravity.

To elucidate the effect of normal gravitation on the shape of the maximum expiratory flow-volume (MEFV) curve, we studied nine normal subjects in a National Aeronautics and Space Administration microgravity research aircraft. They performed multiple MEFV maneuvers at 0, 1, and approximately 2 G. The MEFV curves for each subject were filtered, aligned at residual volume, and ensemble averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the forced vital capacity at 0 G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0 G over about the upper half of the vital capacity. This is similar to the change previously reported during headout immersion and is consistent with the known effect of engorgement of the lung with blood on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points that determine the detailed individual configuration of MEFV curves can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and thus wave speed.

Adult↗

PubMed1991

Ultrastructural appearances of pulmonary capillaries at high transmural pressures.

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.

Animals↗

PubMed1990

Effect of high PaCO2 and time on cerebrospinal fluid and intraocular pressure in halothane-anesthetized horses.

The effects of different arterial carbon dioxide tensions (PaCO2) on cerebrospinal fluid pressure (CSFP) and intraocular pressure (IOP) were studied in 6 male halothane-anesthetized horses positioned in left lateral recumbency. Steady-state anesthetic conditions (1.06% end-tidal halothane concentration) commenced 60 minutes following anesthetic induction with only halothane in oxygen. During atracurium neuromuscular blockade, horses were ventilated, and respiratory rate and peak inspiratory airway pressure were maintained within narrow limits. The CSFP and IOP were measured at 3 different levels of PaCO2 (approx 40, 60, and 80 mm of Hg). The PaCO2 sequence in each horse was determined from a type of switchback design with the initial PaCO2 (period 1), established 30 minutes after the commencement of steady-state anesthesia, being repeated in the middle (period 3) and again at the end (period 5) of the experiment. Measurements taken from the middle 3 periods (2, 3, and 4) would form a Latin square design replicated twice. The interval between each period was approximately 45 minutes. Data from periods 2, 3, and 4 indicated that CSFP (P less than 0.05) and mean systemic arterial pressure increased significantly (P less than 0.05) with high PaCO2. Mean central venous pressure, heart rate, and IOP did not change significantly during these same conditions. Measurements taken during periods 1, 3, and 5 were compared to assess the time-related responses to anesthesia and showed a significant increase in CSFP, a significant decrease in mean central venous pressure, and a small (but not statistically significant) increase in mean systemic arterial pressure.

Animals↗